Any form of invasive examination of the human body presents risks, and requires considerable resources. Assessment of tumors by non-invasive techniques, in order to determine whether a biopsy or surgical removal of the tumor is necessary, is therefore highly desirable.
In our above mentioned previous WO 2012/006431, we describe a Tactile Imaging System that images the size and shape of a tumor or other subsurface inclusion in a solid body by pressing a flexible waveguide against the surface of the body. Light is propagated through the waveguide by total internal reflection (TIR). Distortion of the waveguide by the inclusion breaks TIR, and the escaping light is imaged. The resulting image provides valuable information on the size and shape of the tumor, and if different images are taken at different contact pressures, valuable information can also be extracted regarding the elasticity of the tumor.
In Sahu et al., “Tactile and Hyperspectral Imaging Sensors for Mammary Tumor Characterization,” Proceedings of IEEE Sensors Conference, Baltimore, Md., Nov. 4-6, 2013, and Sahu et al., “Characterization of Mammary Tumors Using Noninvasive Tactile and Hyperspectral Sensors,” IEEE Sensors Journal, Vol. PP, Issue 9, DOI 10.1109/JSEN. 2014. 2323215, May 2014, the present inventor and others showed that combining the tactile imaging with hyperspectral data can characterize tumors more accurately. We obtained tactile data and spectral data from cameras and used a machine classification algorithm to characterize tumors.
Studies have shown that malignant lesions are typically stiffer than benign lesions. A few methods have been proposed for determining the elasticities of tumors. For example, tactile sensors, piezoelectric finger sensor, and elastography. Some of the artificial tactile sensing methods previously proposed use a transduction method to estimate the stress information and obtain elasticity data using a computational model. Commercial palpation imaging systems are available from companies such as Medical Tactile™ Inc. and Assurance Medical™ Inc. These sensors use hundreds of pressure sensors.
Existing spectral imaging sensors acquire multiple spatially co-registered data in many spectral bands; this is a spin-off from NASA's spectral remote sensing technology. Different wavelengths allow the user to obtain different types of information. Recently, spectral cameras are actively being used in medical applications. Near infrared spectral images are used to estimate blood oxygenation levels of a heart. Most spectral systems developed to date are specifically designed for a particular organ such as the brain. Spectral imaging in the near infrared band has also been used in tumor identification for small animals. U.S. Pat. No. 8,320,996 (Panasyuk et al.) has been obtained for hyperspectral imaging for monitoring physiology 2007. Additional information is available in a related paper, S. V. Panasyuk et al., “Medical hyperspectral imaging to facilitate residual tumor identification during surgery,” Cancer Biol. Ther., vol. 6, no. 3, pp. 439-446, 2007. Panasyuk et al. used a spectral microscope to facilitate identification of residual breast tumor in a rat. They successfully differentiated different tissue types. However, the field of view of the system was small (3 cm by 6 cm) and the time required to take the image and analyze is significant.
It has previously been proposed to derive the tissue composition of oxyhemoglobin, deoxyhemoglobin, water, and lipids using spectroscopy. The red band absorption is dominated by deoxyhemoglobin (Hb) with a 760 nm peak, oxyhemoglobin (HbO2) with broad band absorption beyond 800 nm, water with a peak at 970 nm, and lipid with a main peak at 930 nm. Moreover, a spectral camera can determine neoangiogenesis (new vessel formation), which is often associated with cancer. Thus, it is possible to correlate the optical properties with physiological parameters. It has been suggested that spectral information can be used to derive physiological conditions of tissue.
Several research groups have demonstrated the sensitivity of spectral markers of breast cancer. For example, in diseased tissue, measurements of tumor total hemoglobin concentration typically are 2-4 fold greater than in normal tissue, and tumor StO2 (tissue oxygen saturation) values are generally reduced by 5-20%. Water content is also a reliable indicator of tumors such as fibroadenomas. The absorption of oxyhemoglobin and deoxyhemoglobin dominates at the shorter wavelengths (600-850 nm) of the spectral window for optical mammography. The absorption of lipid and water are relevant at longer wavelengths (900-1000 nm). Quantification of oxyhemoglobin concentration [HbO2] and deoxyhemoglobin concentration [Hb] in breast tissue allows for measurements of tissue oxygen saturation StO2=[HbO2]/([HbO2]+[Hb]) and total hemoglobin concentration [HbT]=[HbO2]+[Hb]. The tumor tissue displays increased absorption (decreased reflectance or absorption) in the 650-850 nm spectral range, corresponding to higher tumor total hemoglobin concentration.
The lipid/water ratio is substantially greater for normal tissue, which corresponds to a significant increase in tumor water content. Also, breast tumor tissue has higher scattering values and a steeper scattering slope than normal tissue. This suggests that tumor is composed of smaller scattering particles compared to the surrounding, principally fatty tissue. Overall, the differences in spectra between the two tissue types (malignant vs. benign) are manifestations of multiple physiological changes due to increased vascularity, cellularity, oxygen consumption and edema in malignant tumor.
There is at the time of writing no commercial system for veterinary mammary tumor screening, but spectroscopy-based devices are available for human breast tumor screening, using static laser-based technologies to assess various optical properties of breast abnormalities. ComfortScan of DOBI Medical International (East Windsor, Conn., http://dobiglobal.com/index.htm) uses a dynamic method that applies uniform pressure and detects the differences of the transilluminations due to angiogenesis (growth of new blood vessels).
There is still room for further improvement in the non-invasive characterization of tumors.